Compendium of the most significant studies with reference to properties, intake, effects.

Maiullari E, Bianco ER, Cortese MG, Magro P, Guanà R, Vinardi S, Canavese F. Conservative treatment of children constipation with Macrogol 4,000. Minerva Pediatr. 2008 Aug;60(4):407-10.

Viaud-Quentric K, Lefranc-Jullien S, Feraille L, Elena PP. Long-term tolerance of preservative-free eye drops containing macrogol hydroxystearate as an excipient. J Fr Ophtalmol. 2016 Feb;39(2):156-63. doi: 10.1016/j.jfo.2015.09.011.

Gullapalli RP, Mazzitelli CL. Polyethylene glycols in oral and parenteral formulations--A critical review. Int J Pharm. 2015 Dec 30;496(2):219-39. doi: 10.1016/j.ijpharm.2015.11.015.

Ichijima R, Suzuki S, Esaki M, Sugita T, Ogura K, Kusano C, Ikehara H, Gotoda T. Efficacy of macrogol 4000 plus electrolytes in bowel preparation for colonoscopy in patients with chronic constipation. BMC Gastroenterol. 2021 Oct 19;21(1):387. doi: 10.1186/s12876-021-01976-2.

Taylor RR, Guest JF. The cost-effectiveness of macrogol 3350 compared to lactulose in the treatment of adults suffering from chronic constipation in the UK. Aliment Pharmacol Ther. 2010 Jan 15;31(2):302-12. doi: 10.1111/j.1365-2036.2009.04191.x.

Zhang Z, Zhang Y, Song S, Yin L, Sun D, Gu J. Recent advances in the bioanalytical methods of polyethylene glycols and PEGylated pharmaceuticals. J Sep Sci. 2020 May;43(9-10):1978-1997. doi: 10.1002/jssc.201901340.

Charlton RA, Snowball JM, Bloomfield K, de Vries CS. Colorectal cancer risk reduction following macrogol exposure: a cohort and nested case control study in the UK. PLoS One. 2013 Dec 20;8(12):e83203. doi: 10.1371/journal.pone.0083203.

Wegner A, Banaszkiewicz A, Kierkus J, Landowski P, Korlatowicz-Bilar A, Wiecek S, Kwiecien J, Gawronska A, Dembinski L, Czaja-Bulsa G, Socha P. The effectiveness of Lactobacillus reuteri DSM 17938 as an adjunct to macrogol in the treatment of functional constipation in children. A randomized, double-blind, placebo-controlled, multicentre trial. Clin Res Hepatol Gastroenterol. 2018 Oct;42(5):494-500. doi: 10.1016/j.clinre.2018.03.008.

Guest JF, Candy DC, Clegg JP, Edwards D, Helter MT, Dale AK, Fell J, Cosgrove M, Debelle G. Clinical and economic impact of using macrogol 3350 plus electrolytes in an outpatient setting compared to enemas and suppositories and manual evacuation to treat paediatric faecal impaction based on actual clinical practice in England and Wales. Curr Med Res Opin. 2007 Sep;23(9):2213-25. doi: 10.1185/030079907X210462. Erratum in: Curr Med Res Opin. 2020 Mar;36(3):527.

Zhou T, Zhu L, Xia H, He J, Liu S, He S, Wang L, Zhang J. Micelle carriers based on macrogol 15 hydroxystearate for ocular delivery of terbinafine hydrochloride: In vitro characterization and in vivo permeation. Eur J Pharm Sci. 2017 Nov 15;109:288-296. doi: 10.1016/j.ejps.2017.08.020.

Klimek-Chodacka M, Gieniec M, Baranski R. Multiplex Site-Directed Gene Editing Using Polyethylene Glycol-Mediated Delivery of CRISPR gRNA:Cas9 Ribonucleoprotein (RNP) Complexes to Carrot Protoplasts. Int J Mol Sci. 2021 Oct 4;22(19):10740. doi: 10.3390/ijms221910740.

Macrogol: properties, uses, pros, cons, safety

Macrogol is a chemical compound, polyethylene glycol, PEG, or 1,2-glycol produced through the reaction of ethylene oxide with water, basically non-ionic polymer of ethylene oxide. Macrogol is the international common designation (ICD) used for PEG. 

Macrogol, also known as Polyethylene Glycol (PEG), is a synthetic polymer used in various cosmetic, pharmaceutical, and industrial products. It is valued for its moisturizing, emollient, and stabilizing properties. In cosmetics, Macrogol is used as a base for ointments, a thickener, solubilizer, and humectant. It is often found in skincare products, shampoos, conditioners, creams, and lotions.

Chemical Composition and Structure

Macrogol is a polymer of ethylene oxide, with the general chemical formula H-(O-CH2-CH2)n-OH, where "n" represents the number of ethylene glycol units. Its chemical structure allows it to retain water, making it effective as a humectant and moisturizer. The molecular weight can vary, which influences the physical properties and applications of Macrogol in different products.

Physical Properties

Macrogol can appear as a viscous liquid or waxy solid, depending on its molecular weight. It is soluble in water and many organic solvents, making it an excellent solubilizer and base for ointments and creams. Its water-retaining properties make it useful for enhancing skin hydration, and it also acts as a stabilizer in various formulations.

Production Process

Macrogol is produced by the polymerization of ethylene oxide. The synthesis process allows for control over the molecular weight, which in turn determines the physical properties of the polymer. The different PEG variants, identified by the numbers following the name (e.g., PEG-400, PEG-1000), indicate the molecular weight and define its specific use in different applications.

 It occurs as a fine white powder or transparent colorless liquid.

As a polyether compound it is used:

• in pharmaceutical products (soluble water base, suppositories, topical preparations) as a binding and lubricating additive for tablets, plasticizer in film coating
• in cosmetic and food products for its stabilizing properties.

It is relatively stable and non-toxic

Low molecular weight Macrogol compositions are used by the cosmetic and pharmaceutical industries:

• Macrogol 300
• Macrogol 400
• Macrogol 600
• Macrogol 1000
• Macrogol 1500

Macrogol compositions commonly used by the primarily high molecular weight pharmaceutical industry are targeted for the treatment of constipation (1):

• Macrogol 3350
• Macrogol 4000
• Macrogol 6000

Macrogol 3350 and Macrogol 4000 in gastroenterology, have played an important role, while Macrogol of different molecular weights are used by the pharmaceutical industry as probes to measure mucosal permeability.

Macrogol is widely used in lipsticks, cosmetics, toothpastes with various functionalities: thickener, solvent, lubricant and in medicine inserted in intravenous injections, suppositories.

Although macrogol is generally considered biologically inert, cases of hypersensitivity have occurred (2).

Health and Safety Considerations

Safety in Use
Macrogol is generally considered safe for use in cosmetic and pharmaceutical products. It is well tolerated by the skin and rarely causes irritation or sensitization. However, its safety can vary depending on the molecular weight and concentration in the final product.

Allergic Reactions
Allergic reactions to Macrogol are rare, but they can occur in individuals with specific sensitivities. For people with sensitive skin, it is advisable to perform a patch test before using products containing Macrogol.

Toxicity and Carcinogenicity
Macrogol is considered non-toxic and non-carcinogenic. However, prolonged use and high concentrations of some PEGs in cosmetic and pharmaceutical products have raised concerns due to potential impurities from the manufacturing process, such as dioxane or ethylene oxide, which are considered harmful. Regulatory guidelines require strict monitoring of PEG purity.

Environmental and Safety Considerations
Macrogol is water-soluble and can be biodegradable, but its degradation may take time, particularly at higher molecular weights. Proper disposal is important to reduce environmental impact, especially in industrial applications.

Regulatory Status
Macrogol is widely approved for use in cosmetics and pharmaceuticals in many regions, including the European Union and the United States. However, there are strict regulations on monitoring impurities in PEGs to ensure consumer safety.

Macrogol studies

Typical optimal characteristics of a commercial product

Where to buy Macrogol

• Molecular Formula:  C₁₅H₂₁ClN₂OS      (C₂H₄O)nH₂O  
• Molecular Weight: 312.9 g/mol
• CAS: 25322-68-3      15272-95-4
• UNII FZ46ONU496
• EC Number: 500-038-2
• DSSTox Substance ID:   
• MDL number  
• PubChem Substance ID 
• InChl  1S/C15H20N2OS.ClH/c1-3-17(4-2)10-9-16-15(18)14-11-12-7-5-6-8-13(12)19-14;/h5-8,11H,3-4,9-10H2,1-2H3,(H,16,18);1H
• InChI Key      TZBAVQKIEKDGFH-UHFFFAOYSA-N
• SMILES    CC[NH+](CC)CCNC(=O)C1=CC2=CC=CC=C2S1.[Cl-]
• IUPAC 2-(1-benzothiophene-2-carbonylamino)ethyl-diethylazanium;chloride
• Merck    14,7568 
• NSC 108963

Synonyms: 

• PEG
• Poly(ethylene glycol)
• 1,2-Ethanediol

References____________________________________________________________________

(1) De Giorgio R, Cestari R, Corinaldesi R, Stanghellini V, Barbara G, Felicani C, Di Nardo G, Cucchiara S. Use of macrogol 4000 in chronic constipation. Eur Rev Med Pharmacol Sci. 2011 Aug;15(8):960-6. 

Mínguez M, López Higueras A, Júdez J. Use of polyethylene glycol in functional constipation and fecal impaction. Rev Esp Enferm Dig. 2016 Dec;108(12):790-806. doi: 10.17235/reed.2016.4571/2016.

(2) Wenande E, Garvey LH. Immediate-type hypersensitivity to polyethylene glycols: a review. Clin Exp Allergy. 2016 Jul;46(7):907-22. doi: 10.1111/cea.12760.